Deciphering Adult Neural Stem Cells with Single-Cell Sequencing.

Adult neural stem cells (NSCs) are restricted to the two neurogenic regions of the mammalian brain, where they self-renew and generate progenies of multiple lineages, including neurons, astrocytes, and oligodendrocytes. Single-cell RNA sequencing technology, which reconstructs high-resolution transcriptional landscapes, provides valuable insights into cellular heterogeneity and developmental dynamics. In this review, we overviewed recent progress in the single-cell analyses of both conventional and unconventional NSCs. We discussed the heterogeneity among the stem cell pool and characterized the transcriptional alterations in aging and brain tumors. A comprehensive understanding of NSCs in physiological and pathological settings will provide insights for the rejuvenation of the aged brain and restoration of normal brain function in multiple neurological disorders.

Lens nucleus dislocation in hypermature cataract: Case report and literature review.

INTRODUCTION: Hypermature cataract is a form of late-stage cataract progression that can lead to a variety of complications. Spontaneous capsular rupture with lens nucleus displacement in hypermature cataracts has rarely been reported. We describe 2 cases of spontaneous dislocation of the lens nucleus in a hypermature cataract and perform a review of the literature on this complication. PATIENT CONCERNS: We report 2 rural men aged 50 and 76 years with deteriorating vision. DIAGNOSIS: The final diagnosis was senile hypermature cataract with dislocation of the lens nucleus in both patients and secondary glaucoma for the second patient. INTERVENTIONS AND OUTCOMES: During admission, both patients complained of deteriorating vision. Slit-lamp examination showed lens nucleus dislocation into the anterior chamber. The 50-year-old patient exhibited a residual lens capsule and a turbid cortex, with a normal anterior chamber and intraocular pressure. The 76-year-old patient presented a shrunken and ruptured capsule and no cortex in the pupillary area, mild inflammation in the anterior chamber, and high intraocular pressure. Both patients underwent intracapsular cataract extraction combined with anterior vitrectomy and achieved good postoperative recovery. CONCLUSION: Lens nucleus dislocation in hypermature cataracts can be seen in clinical practice, particularly in underdeveloped areas. Early recognition and surgery can improve vision.

Effects of chronic elevated intraocular pressure on parameters of optical coherence tomography in rhesus monkeys.

AIM: To determine the progression of parameters from optical coherence tomography (OCT) in chronic elevated intraocular pressure (IOP) monkeys. METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer (RNFL) thickness, and parameters from optic nerve head (ONH) analysis were collected before and after laser treatments biweekly for up to 28wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model. RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2wk after elevated IOP induction (P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk. CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.

Role of mitochondria in the pathogenesis and treatment of glaucoma.

OBJECTIVE: To gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma. DATA SOURCES: The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "mitochondria", "glaucoma" and "trabecular meshwork" or "retinal ganglion cells". STUDY SELECTION: Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed. RESULTS: Mitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma. CONCLUSIONS: Mitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage.

Comparison of combined phacotrabeculectomy with trabeculectomy only in the treatment of primary angle-closure glaucoma.

BACKGROUND: Trabeculectomy has become a mainstream treatment in intraocular pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously improve vision for patients with PACG and coexisting cataract. This study was specialized to compare the efficacy and safety of combined phacotrabeculectomy with that of trabeculectomy only in the treatment of PACG with coexisting cataract. METHODS: This is a comparative case series study. Thirty-one patients (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs, and complications were compared at the final follow-up. Complete success was defined as a final IOP less than 21 mmHg without IOP-lowering medication. RESULTS: After 10 months of postoperative follow-up, the phacotrabeculectomy and trabeculectomy groups showed no significant differences regarding IOP reduction ((20.59 ± 7.94) vs. (24.85 ± 14.39) mmHg, P = 0.614), complete success rate (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs. 93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P = 0.380). IOP-lowering medication was not required for most of the patients in both groups. Additional surgery interventions, including anterior chamber reformation and phacoemulsification, were needed in the trabeculectomy group, whereas no surgery was needed postoperatively in the phacotrabeculectomy group. CONCLUSION: Phacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction, successful rates, and complications when it comes to treating PACG patients with coexisting cataract, although additional surgery intervention may be needed for a few cases with cataract and complications after trabeculectomy.

Rehabilitation of vision disorder and improved quality of life in patients with primary open angle glaucoma.

BACKGROUND: Primary open angle glaucoma (POAG) is a common cause of irreversible blindness. The variable etiology of POAG poses significant challenges for treatment and rehabilitation. We analyzed a large POAG patient cohort during treatment to reveal possible causes of vision disorder, assess vision-related quality of life (VRQL), and to evaluate the efficacy of rehabilitative treatments. METHODS: We analyzed the visional disturbances in 500 POAG patients (890 eyes) by regular ophthalmic examination and visual field examination using Humphrey 30° perimetry. Appropriate rehabilitative treatments for POAG were prescribed based on results of clinical examination and included correction of ametropia, health education, counseling, and the fitting of typoscopes. VRQL was assessed before and after treatment by a VRQL self-assessment questionnaire. RESULTS: Scores on the VRQL self-assessment were significantly lower compared to healthy controls. The primary cause of the vision disturbances was ametropia (97.99%), and 51.61% of the ametropia eyes had not received appropriate correction. The secondary causes of visual impairment were glaucomatous neurodegeneration (26.29%), complicated cataract, or other accompanying eye diseases. The causes of the clinical low vision (44 patients) were glaucomatous neurodegeneration (32 eyes), fundus diseases (23 eyes), keratopathy (11 eyes), and other eye diseases (10 eyes). The VRQL scores of patients improved significantly after rehabilitation and the correction of ametropia (P < 0.01). Twenty-five patients with low vision were provided with typoscopes, and 21 (84%) experienced significant functional recovery, while the remaining low vision patients could see letter lines two or more levels lower (smaller) on visual charts in a near vision test. CONCLUSIONS: Vision disorders in POAG patients are common and severe. Appropriate rehabilitation, especially the correction of ametropia, can significantly improve VRQL as revealed by the self-assessment of POAG patients.

Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery.

PURPOSE: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. METHODS: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. RESULTS: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 ±0.05) ng/ml at day 3 to (7.74 ±0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25±3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75±1.71% and 8.50±1.92%) compared to the Group B and D (p<0.01). CONCLUSIONS: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.

Pro370Leu myocilin mutation in a Chinese pedigree with juvenile-onset open angle glaucoma.

PURPOSE: To investigate the genotype and phenotype of juvenile-onset open angle glaucoma (JOAG) in a Chinese family (PN pedigree). METHODS: Each family member was comprehensively examined by an experienced ophthalmologist. The clinical characteristics of the family patients with JOAG were documented. Blood samples were obtained from 22 available participants from the PN pedigree. Linkage analysis was performed to identify the possible chromosome loci. The presence of gene mutation was ascertained by polymerase chain reaction amplification and subsequent direct sequencing. RESULTS: The affected members in the PN pedigree are characterized by early age of onset (mean age at diagnosis is 17 years old), severe clinical presentations, high intraocular pressure (mean IOP of 34.18±2.97 mmHg), and poor response to pharmacological treatment (87.5% of the patients required filtering surgery). The region on chromosome 1 between D1S3464 and D1S1619 was identified in this pedigree by linkage analysis. A Pro370Leu myocilin mutation resulting from a heterozygous C→T transition at the 1,109th nucleotide in exon 3 was detected by gene sequencing. The Pro370Leu mutation co-segregated among all affected individuals of PN pedigree. CONCLUSIONS: The GLC1A Pro370Leu mutation is firmly correlated with a severe POAG phenotype. These data provide clues for the severe disease-causing nature of the Pro370Leu allele. Gene screening may be a useful method for pre-symptom diagnosis and a forewarning to detect the at-risk individuals in familial open-angle glaucoma patients, especially in pedigrees of early-onset.

Comparison of FP-7 and S-2 Ahmed glaucoma valve implantation in refractory glaucoma patients for short-term follow-up.

BACKGROUND: Ahmed glaucoma valves (AGV) has been used for decades, but there is no detailed report about the efficacy of AGV in Chinese glaucoma patients. This study aimed to compare the intraocular pressure (IOP) lowering efficacy and side effects of S-2 polypropylene and PF-7 silicone AGV implantation in Chinese refractory glaucoma patients. METHODS: Patients were divided into S-2 model AGV group and FP-7 model AGV group. The complete and qualified surgical success rate, change of IOP, number of anti-glaucoma medications used and postoperative complications were recorded and analyzed. RESULTS: Average follow-up time was comparable between two groups. IOP was reduced from (37.9 ± 12.7) mmHg preoperatively to (17.3 ± 5.3) mmHg at the last follow-up in S-2 group and reduced from (39.9 ± 14.4) mmHg to (17.7 ± 4.9) mmHg in FP-7 group. Anti-glaucoma medications were reduced from 3.8 ± 0.2 to 1.5 ± 0.2 in S-2 group, and 3.5 ± 0.2 to 0.7 ± 0.2 in FP-7 groups. The cumulative success rates were comparable in two groups, which were 61.2% and 72.1% in S-2 group and FP-7 group respectively. When IOP reduction criteria was used, complete success rates were 30.6% and 51.2% for S-2 and FP-7 groups, and qualified success rates were 86.1% and 92.7% separately. In both groups, the major complication was hypotony, and the previous trabeculectomy of patients was the major risk factor for surgery failure. CONCLUSIONS: In this short-term retrospective study, S-2 AGV is showed at least as effective as FP-7 AGV in IOP reduction, but associated with higher rate of complications. Previous trabeculectomy is a principle risk factor for AGV implantation failure. These clinical outcomes are important for converting use of the FP-7 silicon AGV in Chinese refractory glaucoma patients.

Clinical evidence in concurrence of retinitis pigmentosa and glaucoma.

Glaucoma is rarely complicated by retinitis pigmentosa (RP). To provide clinical evidences for this rare situation, we report the concurrence of these two diseases in two children of a Chinese family. In the present two-child Chinese family without positive history, the older sister presented with bilateral sector RP and coexisting chronic angle-closure glaucoma, and the brother with bilateral whole RP but without coexisting glaucoma. Clinical evidences in concurrence of variants of RP and glaucoma because of possible different gene mutations from the same genetic background represent a rare situation, which may provide clues for future researches in molecular pathogenesis of these rare diseases.

Inhibition of latrunculin-A on dexamethasone-induced fibronectin production in cultured human trabecular meshwork cells.

AIM: To determine the effects of a low dose latrunculin (LAT)-A on dexamethasone (Dex)-induced upregulation of extracellular matrix proteins fibronectin (FN) in cultured human trabecular meshwork (HTM) cells. METHODS: HTM cells were cultured to confluent and incubated with 0.4µmol/L Dex and/or 0.05µmol/L LAT-A. FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy. RESULTS: Dex up-regulated FN production in HTM cells, failed to do so when co-incubated with LAT-A. LAT-A decreased production of FN in cultured HTM cells. CONCLUSION: This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma. It has an important prospect as an intraocular pressure- lowering drug.

[Clinical efficacy and safety of FP-7 Ahmed glaucoma valve implantation in neurovascular glaucoma patients].

OBJECTIVE: To evaluate the efficacy and safety of FP-7 Ahmed glaucoma valves (AGV) implantation in neurovascular glaucoma (NVG) as the first choice of surgery. METHODS: This retrospective, comparative case series study collected a total of 36 eyes of 36 patients with neurovascular glaucoma who underwent AGV implantation in Zhongshan Ophthalmic Center from January 2009 to June 2010. Change of intraocular pressure (IOP), the best corrected visual acuity, numbers of anti-glaucoma medication, success rate and postoperative complications were followed up at day 1, week 1, month 1, and every 3 months after surgery. Complete success of surgery was rated as reduction of IOP ≥ 30% without medication and those who failed to meet criteria was rated as partial success. Data were analyzed by paired Student t-test for IOP, rank sum test for paired non-parametric numbers of medication, and repeated measures analysis of variance for comparison of IOP between different time points using SPSS 13.0. RESULTS: Compared with pre-operation, IOP was significant (F = 9.26, P < 0.05) decreased after surgery with FP-7 AGV implantation (39.5 ± 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (9.2 ± 8.9), (11.8 ± 3.8), (13.7 ± 4.8), (16.9 ± 5.3), (16.9 ± 6.8) mm Hg at day 1, week 1, month 1, month 3 and the last following-up of post-operation, respectively. The numbers of anti-glaucoma medication were significantly (Z = 6.764, P < 0.05) reduced from 4.0 (1-6) of pre-operation to 1.0 (1-3) of post-operation. At the last following up, the complete success rate after FP-7 AGV implantation was 80.6%, and qualified success rate was 91.7%. The postoperative complications including occlusion of the drainage tube, exposure of the drainage tube, shallow anterior chamber and encapsulated cystic blebs around the plate were controlled with additional treatment. CONCLUSIONS: The clinical outcome indicated that the implantation of FP-7 AGV has a stable IOP lowering effect and fewer complications, which can be considered as one of the first choices for management of NVG.

Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis.

BACKGROUND: The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis. METHODS: This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors, by comparing the two groups. RESULTS: The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome. CONCLUSIONS: Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients.

[Long-term effects of non-penetrating trabecular surgery versus trabeculectomy for treating glaucoma].

OBJECTIVE: To evaluate clinical outcomes of non-penetrating trabecular surgery (NPTS) and trabeculectomy surgery (TS) in the treatment of primary open angle glaucoma (POAG). METHODS: It was a case-control study. A total of 63 patients (63 eyes) with POAG were observed retrospectively. Thirty one eyes and 32 eyes underwent NPTS and TS, respectively. Intraocular pressure (IOP), filtration bleb, visual field and post-operative complications were observed for 6-60 months. The CMH χ(2) test was used to analyse the difference of them. RESULTS: After operation, the IOP in the NPTS group were from (13.87 ± 4.88) mm Hg (1 mm Hg = 0.133 kPa) to (24.01 ± 6.55) mm Hg, the IOP in the TS group were from (11.90 ± 4.92) mm Hg to (19.10 ± 7.43) mm Hg. The IOP in the NPTS group was significantly higher than that in the TS group (F = 5.137, P < 0.05). The ratio of sustained filtration bleb of NPTS group after surgery was 25/31 (80.6%), while 6/31 were flat filtration bleb. There were statistically significant difference in the rate of disappearance of filtration bleb between these two groups (χ(2) = 8.129, P < 0.05). The difference of visual field loss postoperatively between these two groups was not statistically significant. The incidence rate of newly developed cataract after NPTS and TS was 6/31 and 12/32, respectively. The difference of rate of complication between these two groups was statistically non-significant (χ(2) = 3.797, P < 0.05). The successful rate after NPTS and TS was 61.54% (16/26) and 14.29% (4/28), respectively. The difference of successful rate between these two groups was statistically significant (χ(2) = 14.463, P < 0.05). CONCLUSIONS: Both NPTS and TS are effective methods for the treatment of POAG. Postoperative complications after NPTS are less than those of TS, But patients with TS could maintain a lower IOP than those with NPTS. Long-term efficacy of NPTS is uncertain, it's important to choose the suitable surgery to gain a high success rate.

Expression of stromal cell-derived factor-1 in diabetic retinopathy.

BACKGROUND: Neovascularization can cause vision loss in proliferative diabetic retinopathy (PDR) and may be affected by many factors. Stromal cell-derived factor-1 (SDF-1) is a potent stimulator of angiogenesis. The study was aimed to investigate the expression of SDF-1 and its correlation with vascular endothelial growth factor (VEGF) in the eyes with diabetic retinopathy. METHODS: The levels of SDF-1 and VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 41 eyes of 41 patients with PDR and 12 eyes of 12 patients with idiopathic macular hole (IMH). Vitreous fluid samples and fibrovascular preretinal membranes were obtained at vitrectomy. SDF-1 and VEGF were localized using immunohistochemistry. RESULTS: The vitreous concentration of VEGF was significantly higher in eyes with PDR ((2143.7 +/- 1685.21) pg/ml) than in eyes with IMH ((142.42 +/- 72.83) pg/ml, P < 0.001). The vitreous level of SDF-1 was also significantly higher in eyes with PDR ((306.37 +/- 134.25) pg/ml) than in eyes with IMH ((86.91 +/- 55.05) pg/ml, P < 0.001). The concentrations of both VEGF and SDF-1 were higher in eyes with active PDR than in eyes with inactive PDR. Panretinal photocoagulation (PRP) could decrease the SDF-1 levels in the vitreous of PDR patients. The vitreous concentration of SDF-1 correlated with that of VEGF in eyes with PDR (r = 0.61, P < 0.001). The costaining of SDF-1 and VEGF was confined to the vascular components in preretinal membranes. CONCLUSIONS: SDF-1 protein is highly expressed in both the vitreous and preretinal membranes of PDR patients; SDF-1 may be correlated with VEGF in angiogenesis in PDR.

Dexamethasone disrupts intercellular junction formation and cytoskeleton organization in human trabecular meshwork cells.

PURPOSE: Patients reproduce symptoms of primary open-angle glaucoma (POAG) when treated with glucocorticoids (GCs) topically on the eyes. Here we investigated the effects of GCs on junctional protein expression and cytoskeleton organization in primary human trabecular meshwork (TM) cultures to understand the molecular pathologies of POAG. METHODS: Human TM cells from POAG (GTM) and age-matched nondiseased (NTM) individuals were obtained by standard surgical trabeculectomy. Some of the cultures were treated with dexamethasone (DEX), a synthetic GC, at 1-5 x 10(-7) mol/l for 1-7 days. The expression levels of zonula occluden-1 (ZO-1) and connexin43 (Cx43) in TM cells with or without DEX treatment were measured using reverse transcription (RT)-PCR, immunocytochemistry, and western blot analysis. RESULTS: mRNA and proteins of ZO-1 and Cx43 were found in both NTM and GTM cells. ZO-1 and Cx43 were located on the plasma membrane, especially along the border of adjacent cells. ZO-1 had no marked changes in localization in NTM and GTM cells after treatment with 10(-7) mol/l DEX for 48 h, whereas Cx43 appeared to increase in the cytoplasm. mRNA of two ZO-1 isoforms, alpha+ and alpha-, were present in TM cells, and the former was expressed less than the latter. Only ZO-1 alpha- isoform protein was expressed in NTM cells, whereas proteins of both isoforms were found in GTM cells. DEX increased the protein levels of ZO-1 and Cx43 in both NTM and GTM cells. DEX also altered the F-actin architecture and promoted cross-linked actin network formation, the effects of which were more pronounced in GTM cells. CONCLUSIONS: Our findings not only provide molecular insights to the pathogenesis of GC-induced glaucoma but also suggest that junctional proteins ZO-1 and Cx43 as well as F-actin are targets for developing new modalities in glaucoma therapy.

[Gene screening as the forewarning measure to predict glaucoma].

OBJECTIVE: To investigate the effect of gene screening on forewarning and monitoring of familial open-angle glaucoma pedigree. METHODS: Comprehensive ophthalmic examinations were performed in all available family members. The genomic DNA was extracted from peripheral blood. The myocilin gene was amplified and screened for mutations using direct sequencing. All family members were followed up. RESULTS: Among 12 family members, 5 individuals carry a C to T transition in exon 3 resulting in the substitution of proline to leucine (Pro370Leu), and the other 7 individuals did not carry this mutation. Ophthalmic examinations did not show any abnormality in the optic disc, the thickness of RNFL, and visual field parameters in mutation-carriers. During the follow-up, all carriers were diagnosed as open-angle glaucoma. The mean time of presentation of the defect of visual field was 21.6 months and 14.4 months after the changes in RNFL thickness. CONCLUSION: Genetic diagnosis was proven to be a method with high specificity and sensitivity; and can be used for presymptom diagnosis and forewarning in familial open-angle glaucoma pedigree.

Histological and ultrastructural study on the medial canthal ligament of blepharophimosis, ptosis and epicanthus inversus syndrome.

BACKGROUND: Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a rare congenital ophthalmic disorder, characterized by congenital eyelid malformation including bilateral ptosis, shortening of the horizontal eyelid fissure, epicanthus inversus, and increased distance between the inner canthi. In this research, we studied the histological structure and ultrastructure of medial canthal ligament of patients with BPES. METHODS: Thirty patients with BPES who received plastic surgery at the Zhongshan Ophthalmic Center from March 2006 to January 2008 were studied. There were 17 males and 13 females with an average age of (8.73 +/- 3.37) years (3 - 31 years). The medial canthal ligaments of patients were collected during the plastic surgery to analyze the histological structure by hematoxylin and eosin (HE), Congo red, van Gieson's (VG), Masson trichrome and aldehyde-fuchsin staining. The ultrastructures of the medial canthal ligaments were also analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fifteen samples of medial canthal ligament from healthy persons with an average age of (9.02 +/- 3.12) years (6 - 30 years) were collected as a control group. RESULTS: Morphological and histological study showed that the medial canthal ligaments of BPES patients were composed of collagen fibers, a few elastic fibers and striated muscles. The collagen fibers assemblies were disorganized and the fibrous connective tissues were undergoing hyaline degeneration. The karyopycnosis of fibroblasts was located among the collagen fibrils and the numbers of fibroblasts were decreased. Ultrastructural study with SEM showed that the collagen fibers were larger than normal, irregular and loose. Parts of the collagen fibers were broken and had a coarse surface. Ultrastructural study with TEM showed that the fibroblasts had less cytoplasm, fewer organelles and the nucleus displayed pyknosis. CONCLUSIONS: The medial canthal ligament in BPES patients is composed chiefly of collagen fibers. The collagen fibers of medial canthal ligaments in BPES patients are disorganized and hyaline degeneration is present. The study revealed that the medial canthal ligament of BPES patients might have congenital dysplasia.

Phacoemulsification treatment of subjects with acute primary angle closure and chronic primary angle-closure glaucoma.

PURPOSE: To investigate and compare the effects of phacoemulsification as an initial procedure to control intraocular pressure (IOP) in eyes with acute primary angle closure (APAC) and chronic primary angle-closure glaucoma (CPACG) with coexisting cataracts and peripheral anterior synechiae (PAS) of greater than 180 degrees. SETTING: Prospective, cross-sectional study. METHODS: Thirteen patients (13 eyes) with APAC and 10 patients (10 eyes) with CPACG were enrolled in the study. IOP control in the 2 groups was compared at final follow-up. Other outcome measures included visual acuity, anterior chamber depth, gonioscopic appearance, and complications. RESULTS: The postoperative IOP was reduced in both the APAC and CPACG groups. As assessed at last follow-up (median 6 mo), IOP in the APAC group was significantly lower than that in the CPACG group. The absolute success rate was 100% in the APAC group and 80% in the CPACG group. The number of hypotensive medications decreased in both APAC and CPACG group. The postoperative degree of PAS was relieved in 11 of 12 eyes with APAC and 5 of 9 eyes with CPACG. CONCLUSIONS: Initial phacoemulsification performed to provide short-term control of IOP is more efficacious in patients with APAC than in those with CPACG, especially when PAS is greater than 180 degrees.